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Biomedical subjects

C Raffoux

Publications and source records attributed to C Raffoux.

At least 19 recordsLinked to original sources

Hematopoietic stem cell donor registry strategies for assigning search determinants and matching relationships.

Registries and cord blood banks around the world collect and store the HLA types of volunteers in order to identify matched unrelated donors for patients requiring hematopoietic stem cell transplantation. This task is complicated by the many formats in which HLA types are provided by the testing laboratories (types obtained by serology vs by DNA-based methods; high vs intermediate vs low resolution) and by the need to identify which of these diverse types are most likely to match the HLA assignments of a searching patient as closely as possible. Conversion of the assignments to 'search determinants' may be included within the algorithm used to select and prioritize a list of potentially suitable donors, either as an aid to matching or as a tool to optimize the performance of comparisons within large data files. The strategies used by registries to create search determinants are described. A set of search determinants, utilized by the National Marrow Donor Program, is provided as an example and is intended to initiate further discussion aimed at understanding the process used by each registry with the possibility of developing a standard process among registries worldwide.

Algorithms↗

A special report: suggested procedures for international unrelated donor search from the donor registries and quality assurance working groups of the World Marrow Donor Association (WMDA).

This special report details the World Marrow Donor Association's recommended procedures regarding the international search for an unrelated donor for hematopoietic stem cell transplantation. The responsibilities of the national hubs, transplant center and donor registry staff are outlined for all actions associated with the preliminary search, formal search, donor confirmatory typing and final donor selection.

Hematopoietic Stem Cell Transplantation↗

World Marrow Donor Association: international standards for unrelated hematopoietic stem cell donor registries.

World Marrow Donor Association standards are aimed at enhancing the quality of unrelated volunteer donor hematopoietic stem cell registries assisting transplant physicians in the international search for unrelated donors for their patients. The standards cover: (1) general organization of registries; (2) donor recruitment; (3) donor characterization; (4) information technology; (5) facilitation of search requests; (6) second/subsequent donations; (7) collection/processing/transport of stem cells; (8) follow-up of patient/donor; and (9) financial/legal responsibilities.

Biological Specimen Banks↗

Cost-effectiveness analysis of two strategies for typing unrelated donors for bone marrow transplantation in France.

Large Registries of HLA-typed potential volunteer donors have been set up in numerous countries to find HLA-matched unrelated bone marrow donors. This study compared two strategies medicoeconomically for HLA typing in the context of a bone marrow volunteer donor Registry. It investigated the cost-effectiveness of strategies before and after the French Registry was modified in January 1999: HLA- A, B typing only at registration and secondary HLA-DR typing on part of the Registry (AB strategy) vs. typing at once for HLA- A, B, and DR (ABDR strategy). The point of view considered was that of payers, French typing tariffs with a 5% discount rate were used, effectiveness was defined as identification of at least one donor with no HLA-A, B, DR incompatibilities for a given recipient (compatible potential donor), the observation period was 9 months, and the judgement criterion was the differential cost-effectiveness ratio. The ABDR strategy identified 94.7% (142/150) of compatible potential donors. The differential cost-effectiveness ratio between the two strategies was 387,005 francs (Euro 58,995) for one supplementary compatible potential donor. Compared with a "do nothing" policy, the ratio was 3,744,087 francs (Euro 570,745) for the AB strategy vs. 576,136 francs (Euro 87,826) for the ABDR strategy. The ABDR strategy is thus more effective but also more costly than the AB strategy. Nevertheless, because of its lower effectiveness and the size of available ABDR Registries, the AB strategy will become obsolete.

Journal Article↗

DPB1 disparities contribute to severe GVHD and reduced patient survival after unrelated donor bone marrow transplantation.

In order to evaluate the impact of HLA-DBP1 incompatibilities on the occurrence of acute graft-versus-host disease (GVHD) in unrelated hematopoietic cell transplantation, we studied 57 donor/recipient pairs characterized by their allelic identity for HLA-A, B, C, DRB1 and DQB1 and also for DRB3, 4, 5 loci and aimed to correlate DPB1 mismatches to already described risk factors for GVHD using multivariate Cox regression analysis. DPB1 identity between donor and recipient was observed in 24% and DPB1 compatibility (GVHD vector) in 42%. Two factors were independently associated with severe acute GVHD: two DP incompatibilities (RR = 8.25, 95% confidence interval (CI): 1.67-40.10, P = 0.010) and disease risk (RR = 10.23, 95% CI: 1.12-93.13, P = 0.012). Two DPB1 incompatibilities appeared also to be a factor in poorer survival independent of its effect on acute GVHD (RR = 4.97, 95% Cl: 1.80-13.71, P = 0.002). A correlation between acute GVHD and matching for each individual DPB1 polymorphic region and for residue 69 of the DP beta molecule, which seems to be a key residue in the alloimmune response, was not observed. Our data indicate that the outcome of unrelated hematopoietic cell transplantation in terms of GVHD but also survival, could be improved through HLA-DPB1 matching or at least by avoiding two DPB1 mismatches.

Adolescent↗

HLA class I and class II are both associated with the genetic predisposition to primary Sjögren syndrome.

Primary Sjögren syndrome (pSS) is an autoimmune disease characterized by progressive destruction of the exocrine glands leading to mucosal and conjunctival dryness. It is marked by lymphocytic infiltration of the glands and the accumulation of several types of autoantibodies such as rheumatoid factor (RF), antinuclear, anti-SS-A (anti-Ro) and anti-SS-B (anti-LA) autoantibodies. The susceptibility to pSS and/or the presence of SS-A/SS-B autoantibodies in pSS patients is associated with DRB1*03-DQB1*02 and DRB1*02-DQB1*06 haplotypes, whereas no associations have been described with any HLA class I allele. To define the impact of HLA class I alleles in predisposition to pSS, 46 patients responding to the European criteria and 222 healthy unrelated Caucasians were analyzed for their HLA class I and class II haplotypes. Our results confirm the association of the DRB1*03-DQB1*02 haplotype with SS-A/SS-B autoantibodies positive pSS and demonstrate a significant association of the HLA-A24 with the disease. Moreover, HLA-A24 is more often associated with DRB1*11-DQB1*0301 and/or DRB1*0301-DQB1*02 in pSS patients than in the controls. The novel association of HLA class I alleles with susceptibility to pSS provides new insights to the genetic predisposition to this disease and subsequently to its physiopathology.

Adult↗

A novel HLA-B*51 allele (B*5116) identified by nucleotide sequencing.

We report here an additional HLA-B*51 variant designated HLA-B*5116. Detected by an abnormal serological reactivity pattern, this variant was identified as a B*51 allele by polymerase chain reaction using sequence-specific primers (PCR-SSP) and characterized by nucleotide sequencing. The new variant sequence match closely with the classical HLA-B*5101 excepted two adjacent nucleotide substitutions at positions 216 and 217 of the third exon and the subsequent Leucine to Glutamic acid change at codon 163 of the alpha2 domain (CTG-->GAG). This new variant was not detected in three different ethnic groups (French, Algerian and Lebanese) suggesting a very rare frequency.

Alleles↗

A novel HLA-B null allele (B*4022N) generated by a nonsense codon in the alpha1 domain.

We describe in this work a novel HLA-B null allele designated B*4022N. This new variant was found in a Caucasian individual who was serologically typed for one HLA-B allele as a B-blank, Bw-blank. Retrospective DNA typing by polymerase chain reaction using sequence-specific primers (PCR-SSP) has established the correspondence of this blank allele with the classical HLA-B*4001 allele. Nucleotide sequence analysis of exon 2 and 3 has revealed the presence of two adjacent point mutations at position 170 and 171 of exon 2 (GG to TT). While the first difference is silent, the second leads to the creation of a nonsense codon at position 58 of the alpha1 domain, providing the most likely mechanism underlying the observed null phenotype.

Alleles↗

A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.

The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.

Bone Marrow Transplantation↗

A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors.

The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/ split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.

Hematopoietic Stem Cell Transplantation↗

Characterization of a novel HLA-Cw*04 variant in a Laotian family: HLA-Cw*0406.

The sequence of a new HLA-Cw*04 allele has been identified in a Laotian family. This allele, designated Cw*0406, differs from Cw*0403 by a single nucleotide substitution at codon 156 (CGG-->CTG) in the alpha2 domain, leading to an amino acid change from Arginine to Leucine. Further screening by specific amplification of two ethnically different populations, i.e. French (n=150) and Lebanese (n=100), provided no case of Cw*406, suggesting that the distribution of this allele may be restricted.

Alleles↗

Histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors: report from The World Marrow Donor Association. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.

The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. The ability to identify unrelated stem cell donors in one country for patients in another country requires cooperation and standardization in many areas. The adoption of guidelines for histocompatibility testing, such as those summarized in this report, will facilitate these opportunities and rapidly provide accurately typed donors for patients in need.

Adult↗

Molecular characterization of antigen-processing function in nasopharyngeal carcinoma (NPC): evidence for efficient presentation of Epstein-Barr virus cytotoxic T-cell epitopes by NPC cells.

Potentiation of the EBV-specific CTL response by immunization with CTL epitopes has been proposed as a logical approach for immune-targeting nasopharyngeal carcinoma (NPC) cells in vivo. This approach will undoubtedly be influenced by the ability of these malignant cells to endogenously process and present target epitopes on their cell surface for immune recognition by CTLs. Analysis of NPC cells in fresh tumor biopsies and long-term, established NPC tumors in nude mice revealed normal expression of the MHC-encoded putative peptide transporters TAP1 and TAP2, as well as the proteasome components LMP2 and LMP7, which have been shown previously to be essential components of the class I processing pathway. Moreover, these tumor cells also showed high levels of HLA class I alleles on the cell surface, suggesting that peptides are available for binding to nascent MHC molecules in the endoplasmic reticulum. Using a recombinant vaccinia virus to transiently express the EBV nuclear antigens, we studied the antigen-processing efficiency of NPC cells. Our findings demonstrate that, in contrast to cells from another EBV-associated malignancy, Burkitt's lymphoma, NPC cells display normal antigen-processing function and are efficiently recognized by HLA class I-restricted, virus-specific CTLs. These studies also provide a rationale for focusing on strategies designed to activate CTLs specific for EBV antigens that are expressed in NPC cells in vivo.

ATP-Binding Cassette Transporters↗